4hkp

Crystal structure of human orotidine 5'-monophosphate decarboxylase complexed with CMP-N3-oxide

spinqualitylabelsall models 4hkp, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hkp is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: 16B, GOL, TKW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease UMPS_HUMAN Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM:258900. A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. Function UMPS_HUMAN Publication Abstract from PubMed Orotidine-5'-monophosphate decarboxylase (ODCase) is an interesting enzyme with an unusual catalytic activity and a potential drug target in Plasmodium falciparum, which causes malaria. ODCase has been shown to exhibit unusual and interesting interactions with a variety of nucleotide ligands. Cytidine-5'-monophosphate (CMP) is a poor ligand of ODCase, and CMP binds to the active site of ODCase with an unusual orientation and conformation. We designed N3- and N4-modified CMP derivatives as novel ligands to ODCase. These novel CMP derivatives and their corresponding nucleosides were evaluated against Plasmodium falciparum ODCase and parasitic cultures, respectively. These derivatives exhibited improved inhibition of the enzyme catalytic activity, displayed interesting binding conformations and unusual molecular rearrangements of the ligands. These findings with the modified CMP nucleotides underscored the potential of transformation of poor ligands to ODCase into novel inhibitors of this drug target. Novel cytidine-based orotidine-5'-monophosphate decarboxylase inhibitors with an unusual twist.,Purohit MK, Poduch E, Wei LW, Crandall IE, To T, Kain KC, Pai EF, Kotra LP J Med Chem. 2012 Nov 26;55(22):9988-97. doi: 10.1021/jm301176r. Epub 2012 Oct 18. PMID:22991951 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoribosyltransferase 3D structures Uridine 5'-monophosphate synthase 3D structures

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